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L0301P73 - Adaptive Immune System
__TOC__ Phases of the Adaptive Immune Response *after infection, innate immune responses occur first *dendritic cells (DC) **phagocytose the pathogen and display a peptide on the MHC Class II markers **migrate to the local lymph node **undergo maturation resulting in more receptors and accessory molecules on the surface to interact with B/T cells *at the lymph node, receptor-ligand interactions between DC and B cells, and DC and T cells activating the lymphocytes *B/T cells undergo **clonal expansion (making copies of itself) = swollen lymph nodes **differentiation forming different antibody producing cells and effector T cells *elimination of antigens via: **humoral response - immunoglobulins **cell-mediated response - cytotoxic T cells *apoptosis occurs leaving behind memory cells for subsequent infections x-axis - time can vary for different infections Terminology Antigen Location *in the lymph **originates from epithelium and connective tissue and transported to the lymph node *in the blood **captured in the spleen Initiation of Adaptive Immune Responses *dendritic cells **carry antigen to the secondary lymphoid organs i.e. lymph node, spleen, mucosal associated lymphoid tissue **up-regulate co-stimulatory molecules **present processed antigen to naive T cells - recognise MHC/peptide marker via the antigen-specific T cell receptor (TCR) *activated T cells proliferate and differentiate into effector T cells (helper, cytotoxic) *naïve B cells **activated in lymph nodes by binding of antigen to the B cell receptor (BCR) ***note that B cells can only recognise the antigen itself and not processed components of the pathogen ***process by which DC present to B cells in currently unknown **proliferate and differentiate into antibody-secreting plasma cells *effector T and B cells can then migrate to the site of infection Humoral vs Cell-Mediated Immunity Humoral *naive B cell —> plasma cell —> antibodies Cell Mediated *helper (CD4) T cell **activate macrophages to kill microbes **switches on cytotoxic (CD8) T cell Lymphocyte Receptors B Cell Receptor (BCR) *also known as antibody, immunoglobulin *has a Y shape *many present on each cell, but all of the same type (specificity) *recognises the entire antigen T Cell Receptor *straight receptor that cannot be secreted *CD4 - detects linear peptide epitopes in a MHC Class II marker on an APC *CD8 - detects non-self peptides in MHC Class I marker on an APC Structure of Antibodies *two identical heavy chains - red and blue *two identical light chains - green *identical antigen binding sites on both arms *each have 6 complementarity determining regions (CDRs), i.e. 3 per chain, which allow for high specificity **CDR 3 has the highest variability *different isotopes/classes have different Fc regions (stalks/constant regions) Receptor Somatic Recombination *recombination of DNA allows for production of highly variable and specific receptors *including the BCR heavy chain, BCR light chain, TCR alpha chain and TCR beta chain Example: BCR Heavy Chain *same germline DNA is found in every cell, including immature lymphocytes (do not have receptors on their surfaces yet) *cassettes/Segments of DNA: **V - variable **D - diversity **J - joining **Cμ - constant (for each class) Process *after activation to proliferate/differentiate, random pairing of D and J segments occurs *in the two clones, DJ pairs will combine with a random V segment *VDJ groups then undergo transcription producing RNA *RNA undergoes splicing where VDJ combines with the Cμ segment High Variability *due to recombination of V, D, J segments *due to small addition/subtraction of nucleotides are the areas of recombination between V and D, and D and J Other Receptors *BCR light chain - V and J segments only *TCR alpha chain - V and J segments only *TCR beta chain - V, D and J segments B Cell Development #stem cell #pro-B cell #pre-B cell - heavy chain of receptors are on the membrane surface #immature B cell - IgM expressed on surface of the membrane mature B cell #IgM and IgD expressed on surface Maturation and Selection of Lymphocytes *to-be lymphocytes mature in bone marrow *selection occurs into bone marrow for B cells and thymus for T cells *developing receptors are checked for whether they are self-reactive **if strong recognition with antigen (self MHC) then negatively selected **if weak recognition with antigen then positively selected *negative selection/death occurs when: **cell cannot produce receptor **cell produces an auto-reactive receptor Humoral Immune Responses *naive B cell recognises the microbe **further stimulated by helper T Cell *clonal expansion - activated B cell rapidly proliferates and differentiate *antibody secretion - effector plasma cells **secrete IgM for initial response *isotope switching - IgG is expressed *affinity maturation produces high affinity B cells which secrete high affinity IgG **also produces memory B cells Antibody Isotope Switching *mature B cells can produce different classes of antibodies (Ig) *Ig class is determined by the cytokine “help” received from Th cells *different classes have different functions Major Histocompatibility Complex Markers *Class I - found on all self cells *Class II - found on antigen presenting cells Major Histocompatibility Complex Genes *encodes the molecule that is found on the surface of all cells *MHC are polygenic and polymorphic **class I has three gene loci (A, B, C) ***alleles are inherited from parents **class II has numerous gene loci ***most polymorphic gene in the human genome - alleles vary greatly Structure of MHC Class I *membrane-bound heavy chain and non-membrane bound light chain Class II *membrane bound α and β chain T Cells Maturation and Selection *occurs in the thymus Effector Functions *many subsets of mature T cells *each has a different role in active immunity *vary according to their surface receptors cytokine production *e.g.: **CD4 - Th1, Th2, Th17, Treg, NKT **CD8 - CTL, MAIT Intracellular Processing Pathways Antigen Presenting Cells *express MHC Class I and Class II Process of Presenting Antigen Dendritic Cells, Macrophages *takes in the antigen via endocytosis *processes and breaks down the antigen *synthesises MHC *joins the processed antigen (peptide) and attaches it to the MHC marker *displays the MHC-peptide marker on the cell to initiate an immune response **class II activates CD4 (Th) cells **class I activates CD8 (Tc) cells Normal Cells *if infected by a virus, cytosolic protein is processed instead by a proteasome *peptide is displayed on a class I MHC